Natural phytonutrients, bioactives and antioxidants (“bioactives”) are used in the nutraceutical and pharmaceutical industries for their health benefits. For example, polyphenols from grape seed, pine bark and garlic are used in nutraceutical formulations. There are also several potent bioactives present in rice bran and rice germ oil. The unsaponifiable fraction (i.e., the non-fat portion) of rice oil has a high concentration of useful micronutrients and antioxidants such as tocopherols, tocotrienols, γ-oryzanol, phytosterols, polyphenols and squalene, when compared to other vegetable oils. Several clinical studies with rice bran oil (RBO) demonstrated significant hypocholesterolemic, hypolipidemic and anti-atherogenic properties; see, e.g., Table 1.
TABLE 1Selected RBO clinical studiesPara-ReadingChangeMethodologymeters(mg/dl)(%)ReferenceRice Bran Oil atTotal219-177−19Lichtenstein, A. H,60 g/dayCholes-et al. (1994) “Rice15 moderatelyterolBran oil consumptionhypercholes-LDL-C162-122−25and plasma lipid levelsterolomic subjects.HDL-Cnonoin moderately hyper32 days, doublechangechangecholesterolemicblind crossoverTriglyc-131-109−17humans.” Arterio-latin square designeridesscelorsis &along with canola,Thromobosis v. 14corn and olive oils.549556Rice Bran Oil atTotal247-183−25Raghuram, T. et al.35 g/day. 12 hyper-Choles-(1989) “Studies oncholesterolemicterolhypolipidemic effectssubjects.Triglyc-349-212−35of dietary Rice Bran30 days, with aeridesOils in humans.”control group of 9Nutrition Reportshyper-cholester-International v. 39(5):olemic subjects with889-895peanut oil.Rice Bran Oil atTotal194-164−15Suzuki, S. & Oshima,60 g/day. 50 healthyCholes-S. (1970) “Influencefemales of normalterolof blending of ediblecholesterol.Total164-121−26fat and oils on serum7 days withoutCholes-cholesterol levels.blend.terolJapanese J.7 days blend withTotal194-164−19Nutrition v. 28(1):Safflower Oil (SO).Choles-Part 1 pp. 3-6; Part 2At RBO:SO ofterolpp. 194-196.70:30At RBO:SO of85:15
These beneficial properties are attributed to the potent phytonutrients, micronutrients and antioxidants present in the unsaponifiable fraction of the oil (see, e.g., Table 2.) The individual constituents of the rice bran oil unsaponifiable fraction have been well studied for their hypolipidemic, hypoglycemic, hypocholesterolemic, antioxidant and other health benefits in animals and in human subjects.
TABLE 2Selected study on RBO unsaponifiable fractionReadingsFinalLipidInitialUSF/RBOChangeMethodologyParameters(mg/dl)(mg/dl)%References0.4% RBO Un-SaponifiableTotal374243/288 −35/−23Sharma, S. D. andFraction (USF) vs.CholesterolRukmini, C.; Indian J.equivalent 10% Rice BranLDL/VLDL331195/240 −41/−27.5Med. Res. 1987 Mar;Oil (RBO) studied in ratesHDL 43 48/4811.6/11.685: 276-81for hypcholesterolemiceffectUnsaponifiable fraction:TotalNo changeHa, T., Han, S., Kim,277.7 mg/g γ-oryzanol,cholesterol,S., Kim, I., Lee, H.,89.99 mg/g phytosterols,TriglyceridesNo changeand Kim, H., (2005)11.66 mg/g tocols, 3.36HDL-CIncreaseNutrition Research 25:mg/g squalene, 0.73 mg/g597-606.of octocosanolUnsaponifiable fractionTotalDecreasedLee, J., Lee, S., Kim,.cholesterolM., Rhee, C., Kim, I.,LDL-CDecreasedand Lee, K (2005) J.TriglyceridesDecreasedSci. Food. Agri 85:HDL-CNo change493-498.
Antioxidant defense mechanisms in biological systems play a major role in the prevention of a number of diseases such as cardiovascular, cerebrovascular, carcinogenic, and other metabolic age-related disorders. Free radicals, such as singlet oxygen, are highly reactive, attack cellular components, can damage DNA, and alter normal metabolism, resulting in a disease state. Humans are under constant challenge by free radicals; unless charged with sufficient antioxidants to quench these free radicals, the pace of damage to the body is increased and can result in various disease states. Antioxidants provide a defense mechanism and help in preventing and arresting the progression of diseases. It is a constant battle to maintain the delicate balance between oxidants and antioxidants in the body. Epidemiological evidence is mounting on the significant role of natural antioxidants and their vital role in maintaining health and preventing diseases.
Cardiovascular disease (CVD) is a leading cause of mortality in the United States and in developed countries around the world. The disease is linked with well-defined risk factors, such as lipid anomalies, arterial hypertension, diabetes, obesity and smoking. The estimated breakdown of the CVD patient population is as follows: High blood pressure: 50.0 million; Coronary heart disease: 13.9 million; Congestive heart failure: 4.7 million; Stroke: 4.0 million; Rheumatic heart disease: 1.8 million.
There is an increasing need to contain this disease effectively without exponentially increasing the associated healthcare costs. Prescription medications alone will not suffice in addressing this need as they have a high direct and indirect cost. Beyond cost, there are also significant side effects associated with prescription drugs and medical practitioners are reluctant to increase dosages unless absolutely needed. For example, statin drugs for lowering cholesterol are effective, but can have undesired side effects.
Rice bran oil (RBO) is obtained from rice bran, i.e., the mesocarp of paddy. RBO is different from other vegetable oils, which are obtained from the seed and/or nuts. Palm oil, coconut oil, olive oil and rice bran oil are obtained from the mesocarp of the fruit. These oils are rich in several natural antioxidants. However, when these oils are processed to an edible grade during normal refining steps, the valuable bioactive micronutrients and antioxidants contained in the unsaponifiable fraction of the oil are degraded or destroyed during normal refining steps, thus reducing both the bioactivity of the micronutrients and antioxidants and their therapeutic benefit. Obtaining a bioactive micronutrient and/or antioxidant-rich rice oil derivate has posed significant challenges to the oil technologist.
Conventional edible oil refining processes yield several by-products, including soap stock, distillate and gums. These by-products contain high concentrations of several of the vegetable oils' unsaponifiable constituents. Although technologies are available for isolating desirable individual constituents and actives, e.g., tocopherols, tocotrienols and γ-oryzanol, etc., in the unsaponifiable fractions of rice bran and other vegetable oils, the art has not advanced far enough in developing therapeutic applications of suitable natural whole food extract concentrates containing such micronutrients, e.g., in the unsaponifiable fraction of vegetable oils.
Although the components of the unsaponifiable fraction of rice bran oil has been reported for its cholesterol reducing property, the dose at which the individual components give the desired effect is very high. Rice bran oil and palm oil is the predominant natural source of tocopherols and tocotrienols (tocols), however, phytosterols are available in several vegetable oils.
γ-oryzanol is unique to rice bran oil among natural products. It occurs in the highest concentration in the bioactives of the unsaponifiable fraction of rice bran oil. γ-oryzanol is a mixture of at least five components. These five components include ferulic acid esters of cycloartenol, 24-methylene cycloartanol, β-sitosterol, 4-methylsterol and methyl ferulate. γ-oryzanol is a potent antioxidant (Joseph Bruno “The facts on γ-oryzanol” 1987), demonstrated to have UV-quenching properties, and activity on the hypothalamus, relieving stress by increasing DHEA levels and reducing cortisol levels. In addition, it has been reported to induce fat burning that results in lean body mass. Furthermore, it has been shown to have hypocholesterolemic activity, dissolving aortic streaks (Seetharamiah, G. et al., Atherosclerosis 78: 219-223) and dissolving blood clots. It has also demonstrated beneficial effects on cardiovascular risk factors.
U.S. Pat. No. 5,660,691 discusses isolating tocopherols and tocotrienols from rice distillate. U.S. Pat. No. 5,288,902 discusses isolating γ-oryzanol, another valuable antioxidant, from the soap stock, which is typically discarded as a waste product. However, in these techniques and others, the natural matrix is disrupted, and thus the potency and bioavailability of these components is diminished.